The purpose of these studies is to elucidate the mechanisms whereby the Brattleboro homozygous (DI) rat -- which lacks vasopressin -- is able to produce hypertonic urine when deprived of drinking water. The rats are surgically prepared with indwelling catheters such that clearance experiments can be run on animals in the unanesthetized state. Measurements of GFR, and renal blood flow and the renal handling of sodium, potassium, urea and total solute are gathered. The respective influences of the renin-angiotensin, prostaglandin, and adrenergic systems are being evaluated with the use of appropriate blocking agents. In other experiments the corticopapillary gradient is being examined with respect to the nature of the solutes and the time course of the changes during prolonged dehydration. Changes in the topography of the apical membrane of collecting duct cells -- which may reflect changes in water permeability -- are being sought in dehydrated DI rats by freeze fracture techniques. The possible role of oxytocin -- a hormone that the DI rat secretes in excess of normal -- in the development of the corticopapillary gradient and the ability to concentrate urine is also under study.